VitC may act as a scavenger against reactive oxygen species (ROS) and as a chelator, for example, iron metabolism. It plays crucial roles both for the proper function of healthy organs and tissues and for tissue repair and regeneration. Vitamin C, in humans, must be introduced by daily intake through diet. Oxalate is one of the major end products of VitC breakdown in humans, and this may cause accumulation of calcium oxalate stones and nephrocalcinosis thus, susceptible people should avoid systematic ingestion of vitamin C supplements. The main route of elimination of VitC and DHA is urinary excretion (Figure 1).

VitC is continuously catabolized by oxidation to dehydroascorbate (DHA), which in turn is converted into oxalic acid. Its level is maintained in a range between micromolar in the blood plasma (~50 ОјM) and millimolar (~1вЂ“10вЂ‰mM) inside the cells (Figure 1), with the highest levels found in pituitary and adrenal gland cells where it is accumulated through the activity of highly specific transport systems encoded by the SLC23A1 and SLC23A2 genes, also known as SVCT1 and SVCT2. Humans are unable to synthesize VitC due to the lack of the L-gulonolactone oxidase (GLO) enzyme and therefore are strictly dependent on an exogenous source of VitC. VitC is a naturally occurring small carbohydrate (3-keto- L-gulofuranlactone) synthesized by a two-step reaction mainly from L-galactose or D-galacturonic acid in green plants.

$ecm biology$

In this review, we will focus on the recent progress made on the influence of VitC on stem cell biology and its implications for regenerative medicine. The strong biological, biotechnological, and medical significance of VitC-dependent molecular mechanisms become even more relevant taking into account another key VitC-dependent cellular modification, that is, collagen hydroxylation, which is the most abundant posttranslation modification found in the human proteoma. VitC enhances somatic cell reprogramming, that is, the generation of induced pluripotent stem cells (iPSCs), and pushes embryonic stem cells toward a naive state of pluripotency by modulating the cellular epigenetic profile.

Specifically, VitC has emerged as a key regulator of stem cell identity/behavior, influencing pluripotency, self-renewal, and differentiation. In the last years, the use of cutting-edge technologies (next-generation sequencing and advanced microscopy) to study stem cell biology have broadened enormously our knowledge of VitC activities. It is only until recently that ECM homeostasis was considered the unique molecular mechanism influenced by VitC availability. Indeed, under VitC deprivation, human cells are unable to generate and maintain healthy tissues, in particular those rich in collagens such as the skin, bones, and cartilage, and VitC deficiency in humans causes scurvy, a complex syndrome characterized by generalized ECM dissolution and tissue disintegration. Human cells are unable to synthesize VitC, and therefore, it must constantly be restored through the diet.

L-Ascorbic acid (vitamin C (VitC)) was extensively studied over the last century because it plays an essential role for proper folding and deposition of collagen proteins, which are the most abundant proteins in the human body and have a strong impact on the composition/structure/biomechanical features of the extracellular matrix (ECM). The broad spectrum of actions of VitC highlights its relevance for stem cell biology in both physiology and disease. In the nucleus, VitC enhances the activity of DNA and histone demethylases, improving somatic cell reprogramming and pushing embryonic stem cell towards the naive pluripotent state. Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum, VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons. Here, we review the main functions of VitC and its effects on stem cells, focusing on its activity as cofactor of Fe +2/ О±KG dioxygenases, which regulate the epigenetic signatures, the redox status, and the extracellular matrix (ECM) composition, depending on the enzymesвЂ™ subcellular localization. L-Ascorbic acid (vitamin C (VitC)) has gained growing interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. Transcription factors and signaling molecules are well-known regulators of stem cell identity and behavior however, increasing evidence indicates that environmental cues contribute to this complex network of stimuli, acting as crucial determinants of stem cell fate.

Ecm biology